Upregulation of SIRT1 by 17β-estradiol depends on ubiquitin-proteasome degradation of PPAR-γ mediated by NEDD4-1
Protein & Cell
; (12): 310-321, 2013.
Article
in English
| WPRIM (Western Pacific)
| ID: wpr-757809
Responsible library:
WPRO
ABSTRACT
17β-estradiol (E2) treatment of cells results in an upregulation of SIRT1 and a down-regulation of PPARγ. The decrease in PPARγ expression is mediated by increased degradation of PPARγ. Here we report that PPARγ is ubiquitinated by HECT E3 ubiquitin ligase NEDD4-1 and degraded, along with PPARγ, in response to E2 stimulation. The PPARγ interacts with ubiquitin ligase NEDD4-1 through a conserved PPXY-WW binding motif. The WW3 domain in NEDD4-1 is critical for binding to PPARΓ. NEDD4-1 overexpression leads to PPARγ ubiquitination and reduced expression of PPARγ. Conversely, knockdown of NEDD4-1 by specific siRNAs abolishes PPARΓ ubiquitination. These data indicate that NEDD4-1 is the E3 ubiquitin ligase responsible for PPARγ ubiquitination. Here, we show that NEDD4-1 delays cellular senescence by degrading PPARΓ expression. Taken together, our data show that E2 could upregulate SIRT1 expression via promoting the PPARΓ ubiquitination-proteasome degradation pathway to delay the process of cell senescence.
Full text:
Available
Database:
WPRIM (Western Pacific)
Main subject:
Pharmacology
/
HeLa Cells
/
Down-Regulation
/
Up-Regulation
/
Cellular Senescence
/
Protein Structure, Tertiary
/
Amino Acid Motifs
/
Ubiquitin
/
RNA, Small Interfering
/
RNA Interference
Limits:
Animals
/
Female
/
Humans
Language:
English
Journal:
Protein & Cell
Year:
2013
Document type:
Article